This project focuses on preparation of stereochemically and structurally complex libraries of polyketide-like libraries. Libraries will be prepared that bear natural product-like structures, yet contain diversification elements for additional chemical modification. Stereochemical variants of polyketide cores will be made that probe three-dimensional space. These scaffolds therefore will not be limited by the stereochemical restrictions found in biosynthesis, yet will still maintain the same levels of stereochemical purity. Thus, diastereometrically pure polyketide libraries will be prepared in efficient fashion with stereochemistries not found in nature. The project culminates with the preparation of homo- and heterodimeric macrolides that display structural motifs reminiscent of potent antibiotic macrolides, but with novel structural features and stereochemistries. The first section of the project concentrates on the synthesis of linear polypropionate scaffolds resulting from assymmetric crotylation chemistry that will be used as parent building blocks. The second section focuses on the synthesis of libraries of larger macrocyclic scaffolds that resemble polyketide-like natural products. This goal will be accomplished through the development of efficient cyclodimerization sequence.